Search

Our expanding knowledge of the nature and importance of the human microbiota has provided additional impetus to investigate the use of beneficial bacteria to promote improved health. Recent technological developments in both next-generation DNA sequencing and novel bioinformatic analyses have advanced our understanding of the nature of our microbiome and the degree to which its makeup correlates with human health and specific disease states. It is clear that the application of these technologies has the potential to inform the mechanisms of beneficial effects and to identify potentially valuable candidates for intervention. It should be noted, however, that there is a long history of the use of bacteria, initially in the form of naturally fermented foods and later by investigation of the potential roles of individual bacterial strains in disease prevention. For example, the strain Escherichia coli Nissle 1917 was reportedly isolated about 100 years ago from a World War I soldier who, unlike his cohorts, appeared unaffected by bacterial dysentery, and it has remained a subject of study ever since ( 1 ).

In order to cause disease, pathogenic bacteria require specialized means to sense the various microenvironments presented to them in the context of a host and then to regulate the systems required for establishment, persistence, growth, and induction of the pathologies associated with infection. The example presented in this chapter focuses on one such system utilized by Bacillus anthracis during anthrax infections, iron acquisition. Recently, research focused on the acquisition of one such nutrient essential for successful anthrax infections, iron, has come to the fore. The chapter summarizes the various mechanisms used by B. anthracis for obtaining iron, reviews the relative impact of each of these mechanisms on a successful anthrax infection, and presents the transcriptome regulated by low concentrations of iron. Once inside the bacterial cytoplasm, iron is released from heme when the heme monooxygenase, IsdG, breaks down the molecule. Siderophores are high-affinity iron-chelating molecules that are secreted into the extracellular environment, where they scavenge iron from a variety of host sources. B. anthracis produces two siderophores, bacillibactin and petrobactin. Petrobactin is made up of one central citrate flanked by two spermidine molecules, each with terminal dihydroxybenzoic acid residues. Consequently, molecules that inhibit or block iron acquisition, related membrane transport processes, or bacterial iron-based regulation, in general, may prove to be effective new medical counter-measures against anthrax and related infections. It is predicted that as more defined details of the genes, proteins, factors, and mechanisms that regulate iron metabolism become understood, reasonable countermeasure targets will be identified.